Description

Simple

A medication used to manage seizures in patients who have not responded to other anti-seizure medications. May also be used to treat infantile spasms when the benefits outweigh the risk of vision loss.

Clinical

An irreversible GABA transaminase inhibitor used as an adjunct to treat refractory complex partial seizures in patients ≥10 years unresponsive to alternatives. May also be used as monotherapy to treat infantile spasms in infants 1 month to 2 years.

Overview

An analogue of gamma-aminobutyric acid, vigabatrin is an irreversible inhibitor of 4-aminobutyrate transaminase, the enzyme responsible for the catabolism of gamma-aminobutyric acid. (From Martindale The Extra Pharmacopoeia, 31st ed). Off-label uses include treatment of cocaine dependence.

Pharmacology

Indication

For use as an adjunct in treatment resistant epilepsy, refractory complex partial seizures, and secondary generalized seizures. It is also used as monotherapy in infantile spasms in West syndrome.

Pharmacodynamic

Vigabatrin is an anticonvulsant chemically unrelated to other anticonvulsants. Vigabatrin prevents the catabolism of GABA by irreversibly inhibiting the enzyme GABA transaminase. It is an analog of GABA, but it is not a receptor agonist. However, vigabatrin is not a potent inhibitor of GABA-T with a... Read more

Mechanism of action

Vigabatrin increases brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by irreversibly inhibiting enzymes that catabolize GABA (gamma-aminobutyric acid transaminase, GABA-T). Duration of action is determined by rate of GABA-T re-synthesis. Vigabatrin... Read more

Absorption

Rapidly absorbed following oral administration, absorption is comparable between neonates, infants, and children.
Cmax, 50 mg/kg dose, neonates= 14 mg/L;
Tmax, 50 mg/kg dose, neonates = 2.1 hours;
However, extent of absorption is higher and elimination half life is longer in neonates compared to... Read more

Protein binding

Not protein bound

Volume of distribution

1.1 L/kg

Clearance

Infants = 2.4 ± 0.8 L/h;Children = 5.7 ± 2.5 L/h

Half life

Neonates, 50 mg/kg = 7.5 ± 2.1 hours (due to reduced renal function);
Infants = 5.7 hours;
Adults = 7.5 hours;
Elderly = 12 - 13 hours


Route of elimination

Eliminated primarily through renal excretion as unchanged drugs (80%).

Toxicity

LD50, oral, rat: 3000 mg/kg;
Visual field defects may occur following cumulative doses in excess of 2 kg.

Adverse Effects

Contraindications

  • Hypersensitivity:
    • false
  • Regions: US

Food Interactions

    Information currently not available.

Interactions

Type in a drug name to check for interaction with Vigabatrin
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of adverse effects can be increased when Vigabatrin is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthine
Vigabatrin may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of adverse effects can be increased when Vigabatrin is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-Methoxyamphetamine
The risk or severity of adverse effects can be increased when Vigabatrin is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of adverse effects can be increased when Vigabatrin is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanine
Vigabatrin may increase the excretion rate of 6-O-benzylguanine which could result in a lower serum level and potentially a reduction in efficacy.
7-Deazaguanine
Vigabatrin may increase the excretion rate of 7-Deazaguanine which could result in a lower serum level and potentially a reduction in efficacy.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Vigabatrin is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
The risk or severity of adverse effects can be increased when Vigabatrin is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
7,9-Dimethylguanine
Vigabatrin may increase the excretion rate of 7,9-Dimethylguanine which could result in a lower serum level and potentially a reduction in efficacy.
8-azaguanine
Vigabatrin may increase the excretion rate of 8-azaguanine which could result in a lower serum level and potentially a reduction in efficacy.
8-chlorotheophylline
Vigabatrin may increase the excretion rate of 8-chlorotheophylline which could result in a lower serum level and potentially a reduction in efficacy.
9-Deazaguanine
Vigabatrin may increase the excretion rate of 9-Deazaguanine which could result in a lower serum level and potentially a reduction in efficacy.
9-Methylguanine
Vigabatrin may increase the excretion rate of 9-Methylguanine which could result in a lower serum level and potentially a reduction in efficacy.
Acefylline
Vigabatrin may increase the excretion rate of Acefylline which could result in a lower serum level and potentially a reduction in efficacy.
Acenocoumarol
The metabolism of Acenocoumarol can be increased when combined with Vigabatrin.
Acepromazine
The risk or severity of adverse effects can be increased when Vigabatrin is combined with Acepromazine.
Aceprometazine
The risk or severity of adverse effects can be increased when Vigabatrin is combined with Aceprometazine.
Acetazolamide
The risk or severity of adverse effects can be increased when Acetazolamide is combined with Vigabatrin.
Acetophenazine
The risk or severity of adverse effects can be increased when Acetophenazine is combined with Vigabatrin.
7 References
  1. 1 . Gram L, Larsson OM, Johnsen A, Schousboe A: Experimental studies of the influence of vigabatrin on the GABA system. Br J Clin Pharmacol. 1989;27 Suppl 1:13S-17S.PubMed: 2757904
  2. 2 . Browne TR: Pharmacokinetics of antiepileptic drugs. Neurology. 1998 Nov;51(5 Suppl 4):S2-7.PubMed: 9818917
  3. 3 . Lindberger M, Luhr O, Johannessen SI, Larsson S, Tomson T: Serum concentrations and effects of gabapentin and vigabatrin: observations from a dose titration study. Ther Drug Monit. 2003 Aug;25(4):457-62.PubMed: 12883229
  4. 4 . Zwanzger P, Baghai TC, Schuele C, Strohle A, Padberg F, Kathmann N, Schwarz M, Moller HJ, Rupprecht R: Vigabatrin decreases cholecystokinin-tetrapeptide (CCK-4) induced panic in healthy volunteers. Neuropsychopharmacology. 2001 Nov;25(5):699-703.PubMed: 11682253
  5. 5 . Tulloch JK, Carr RR, Ensom MH: A systematic review of the pharmacokinetics of antiepileptic drugs in neonates with refractory seizures. J Pediatr Pharmacol Ther. 2012 Jan;17(1):31-44. doi: 10.5863/1551-6776-17.1.31.PubMed: 23118657
  6. 6 . Clayton LM, Stern WM, Newman WD, Sander JW, Acheson J, Sisodiya SM: Evolution of visual field loss over ten years in individuals taking vigabatrin. Epilepsy Res. 2013 Aug;105(3):262-71. doi: 10.1016/j.eplepsyres.2013.02.014. Epub 2013 Mar 28.PubMed: 23541931
  7. 7 . Hawker DD, Silverman RB: Synthesis and evaluation of novel heteroaromatic substrates of GABA aminotransferase. Bioorg Med Chem. 2012 Oct 1;20(19):5763-73. doi: 10.1016/j.bmc.2012.08.009. Epub 2012 Aug 16.PubMed: 22944334